New therapies for diseases of the bowel are changing lives

Decades ago, I met a surprisingly quiet, withdrawn young man. Surprising because I knew his bright, vibrant wife and wondered what had attracted her to him. He barely participated in conversations even at friendly family gatherings.

Some years later, the same man seemed to have undergone a personality transplant. He was forthright and funny, intelligent and interesting. I asked a mutual friend what could have accounted for the apparent transformation.

The answer: surgical removal of his chronically inflamed colon to treat ulcerative colitis. Once free of painful abdominal cramps, persistent diarrhea, fatigue, nausea and the depression and anxiety that can accompany these symptoms, he came to life. Even having to cope with a colostomy bag did not dampen his newly awakened spirit. Today, this rather draconian treatment is reserved for the very few patients with inflammatory bowel disease — Crohn’s and ulcerative colitis — whose debilitating symptoms don’t respond to a growing number of less invasive modern therapies.

Although many people with chronically inflamed bowels still have surgery, it is nearly always less aggressive, rarely requiring an external pouch to replace a surgically removed colon and rectum.

In 98 percent of patients with ulcerative colitis who must have the colon removed, it is now replaced by an internal pouch, creating a reservoir for stool that is sutured directly to the rectal canal, said R. Balfour Sartor, chief medical adviser to the Crohn’s and Colitis Foundation of America.

“This approach decreases urgency, enabling patients to defer the need to evacuate and reduces the number of stools per day,” Sartor said.

Inflammatory bowel diseases afflict 1.4 million Americans, typically starting in the teenage years and lasting a lifetime. But treatments for these chronic conditions are being transformed, spurred by the decoding of the human genome and a growing understanding of the balance of microbes in the gut and why it goes awry in some people.

As with operative changes for ulcerative colitis, in recent decades, surgery for Crohn’s disease has become less disruptive of normal digestive function. Instead of removing diseased sections of the intestine, Crohn’s patients can have a procedure called strictureplasty, better preserving the body’s ability to absorb nutrients. Strictureplasty involves cutting the diseased area at its midpoint, stacking the two pieces on top of each other, then cutting and reconnecting them lengthwise. The technique, known as Michalessi strictureplasty for the Weill Cornell surgeon Fabrizio Michalessi, has been shown to encourage regression of the disease in the treated area.

“Surgery doesn’t cure Crohn’s,” Sartor said, “but this technique preserves most of the natural function of the small intestine, where nutrients are absorbed.”

Ellen J. Scherl, gastroenterologist at Weill Cornell Medical Center in New York, emphasized that “surgery is a therapy, not a failure of therapy. If doctors persist with medical therapy to avoid surgery, they may be subjecting patientsto chronic flare-ups.”

At the same time, improved medical remedies are fast emerging. Experts in inflammatory bowel disease are working on treatments based on a patient’s genetic makeup, an approach now increasingly used to treat cancer.

Ramnik J. Xavier, chief of gastroenterology at Massachusetts General Hospital in Boston, said that after determining the genomic regions associated with inflammatory bowel diseases (163 genes have been linked to the ailments), “we’re now looking individually to identify certain genes that affect inflammation and the failure of ulcers to heal.”

There are also genetic changes that protect the gut, Xavier said, and targeted molecules could be designed to treat the disease and prevent relapses.

“Ulcerative colitis and Crohn’s are in many ways the poster child for which sequencing the genome is having a tremendous impact,” Xavier said.

Equally important to improved treatment has been understanding how environmental factors like diet and antibiotics can disrupt the balance of microbes in the gut. Some bacteria are protective and keep the gut healthy, while others result in chronic inflammation.

“Antibiotics, which alter the gut microbiome, may be helpful or not,” Scherl noted. Tailor-making antibiotics that attack only harmful bacteria could give protective microbes a chance to dominate. And altering the diet to deny harmful microbes the nutrients they prefer can curb inflammation.

Scherl said that sugars, other carbohydrates and fats can lead to uncontrolled inflammation in the gut of people genetically predisposed to inflammatory bowel diseases. When a flare-up occurs, she said patients “must step back and eat simpler food” — a so-called white diet — until the inflammation subsides.

Sandra C. Kim, pediatric gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio, treats flare-ups in children with what is called enteral therapy, in which they consume a formula that deprives harmful bacteria in the gut of the nutrients they need to produce substances that foster inflammation.

Although Kim acknowledges that the diet is not easy, when followed for eight to 12 weeks it can induce remission of the disease, reduce the risk of relapse and enable the child to grow normally.

Another new approach aims at the movement of inflammatory cells from the blood into the gut. The Food and Drug Administration just approved a drug called vedolizumab, which blocks the movement.

“This is a completely new strategy for treating Crohn’s and ulcerative colitis,” said James D. Lewis, of the University of Pennsylvania Perelman School of Medicine.

Jane Brody

Jane Brody reports on health for the New York Times.

Last modified: June 10, 2014
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